Journal
BONE
Volume 36, Issue 2, Pages 284-291Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.bone.2004.09.022
Keywords
suramin; RANK; osteoclast differentiation
Categories
Ask authors/readers for more resources
Suramin is a naphthalene trisulfonic acid derivative that inhibits osteoclast differentiation and bone resorption in vitro and in vivo; however, the mechanisms underlying this activity have not been studied. Receptor activator of NF-kB (RANK) ligand (RANKL) is a key regulator of osteoclast differentiation and function and this study evaluated the ability of suramin, which has been shown to disrupt protein-protein interactions, to interfere with RANKL functional activity and binding to RANK. Suramin inhibited osteoclastic bone resorption in a calvarial model and inhibited osteoclast differentiation in RANKL-stimulated murine spleen cells and RAW264.7 cells. RANKL-induced second messenger signaling (AKT and p38 MAP Kinase phosphorylation) was completely blocked by 100 mu M suramin. The ability of RANKL to bind to recombinant human RANK-Fc (rhRANK-Fc) was reduced 50% by suramin in an in vitro binding assay. Surface plasmon resonance technology and nuclear magnetic resonance (NMR) were used to evaluate the ability of suramin to bind to rhRANK-Fc. Suramin was found to selectively interact with immobilized rhPANK-Fc chimera in a concentration-dependent manner by Biacore 3000 analysis. Similar results were obtained using saturation transfer difference NMR spectroscopy to demonstrate that suramin binds to rhRANK-Fc, but not IgG(1)Fc or sRANKL. In summary, these findings demonstrate that suramin inhibits sRANKL-induced osteoclast differentiation and suggest that these effects are mediated by suramin binding to RANK and blocking the ability of sRANKL to induce second messenger signaling. (c) 2004 Elsevier Inc. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available